Trial Approval Research Articles

‘COVID impacted my life in so many ways’: a qualitative study of the lived experiences of the COVID-19 pandemic among people of Black ethnicities living with HIV in England

ABSTRACT Objectives COVID-19 disproportionately affected people of Black ethnicities whilst also negatively affecting the health, wellbeing and livelihoods of people living with HIV. This may have been amplified by pre-existing socioeconomic marginalisation, poorer health, and structural racism. Despite being disproportionately affected by the pandemic, little is known about lived experiences of the COVID-19 pandemic within these communities. Given these disparities, this paper explores the lived experiences of the COVID-19 pandemic among people living with HIV and of Black ethnicities in England. Design This qualitative study, comprising five focus group discussions (FGDs) with people of self-reported Black ethnicity, living with HIV in the UK (n = 30). FGDs were conducted between June and August 2022. Topics covered included beliefs and attitudes about COVID-19 (including prevention), COVID-19 information sources and lived experiences. Data were analysed using a reflexive thematic approach. Results Analysis of the data generated several main themes: the collective trauma experienced by Black communities; racial bias influenced by inequitable research; conflicting COVID-19 health messages and medical mistrust; socioeconomic marginalisation including financial hardship; intersecting oppressions such as sexism and ageism; and the overall impact of living with a stigmatising condition such as HIV. Participants additionally found navigating the infodemic, being labelled ‘clinically vulnerable,’ and balancing multiple non-medical needs alongside their cultural, spiritual, and religious beliefs, challenging. Conclusion The COVID-19 pandemic has had profound and enduring multidimensional impacts on the lives of people of Black ethnicities living with HIV. This study reveals how socioeconomic, cultural, behavioural, and biological factors intersected to shape experiences of the pandemic within these communities in the UK. Our data illustrate the lived realities of worsening health and social inequalities due to COVID-19, while at the same time highlighting the central importance of trusted community organisations in mitigating some of these negative impacts. Trial Registration Ethical approval was obtained from the University College London Research Ethics Committee (Project ID/Title: 6698/004).

Response to FDA draft guidance on pediatric IBD drug approval trials: A consensus statement from the IBD Porto Group.

Response to FDA draft guidance on pediatric IBD drug approval trials: A consensus statement from the IBD Porto Group.

Machine learning approach for detection of MACE events within clinical trial data

ABSTRACT Randomized controlled trials (RCTs) are the gold standard for clinical research but may not accurately reflect the impact of medicines in real-world settings. Supplementing RCTs with insights from real-world data (RWD) can address known limitations by including more diverse patient populations, additional types of sites-of-care, and practices more representative of the care most people receive. One current challenge in using RWD is the lack of an algorithmic approach to identifying outcomes. To address this, machine learning models for identifying a frequently used outcome, Major Adverse Cardiovascular Events (MACE), were developed in Clinical Trial Data (CTD). Anonymized CTD sourced from the Medidata Enterprise Data Store were used to develop model features on the condition that they would be useful for labelling MACE events and that they could also be found in RWD. These features were used to train three random forest models to identify each component of 3-point MACE in a patient’s clinical trial journey. Performance metrics for the models are presented (recall = 0.72 [0.07], precision = 0.68 [0.12] - mean, [SD]) along with the top contributing features. We show that the models can be tuned specifically to replicate the adjudication panels’ results and present a cost–benefit analysis for deploying such models in clinical trial settings. We demonstrate the viability of using advanced algorithms for identifying clinical outcomes in prospective clinical trials. Deployment of such models could reduce the resources required to conduct RCTs. Extending such models to RWD would facilitate approval of pragmatic clinical trials for regulatory submissions.

Abstract B006: Qualitative research study on the use of minimal residual disease as an intermediate endpoint in multiple myeloma clinical trials in Saudi Arabia

Abstract Introduction: The U.S. Food and Drug Administration has recently considered minimal residual disease (MRD) as an acceptable accelerated approval endpoint in multiple myeloma (MM). Meta-analysis studies have shown the clinical benefit of MRD negativity in certain hematological cancers such as MM. Objectives: This qualitative research study, with a unique focus on the Saudi context, aims to assess the opinions and experiences of hematology and oncology specialists and consultants in Saudi Arabia. The study is particularly interested in their views on the use of MRD as an intermediate endpoint in early-phase clinical trials for fast-track drug approval by the Saudi Food and Drug Authority in the context of multiple myeloma. This includes assessing the use of MRD in both newly diagnosed and relapsed/refractory MM. The secondary objective is to gather information about the feasibility and availability of sensitive MRD detection methods in real-world medical practice and clinical trials in Saudi Arabia. Study Design: The study will involve interviewing 30 registered male or female physicians specialized in hematology and oncology in Saudi Arabia. The physicians will be included in the study using purposive sampling methods. The study will collect the physicians’ opinions and experiences about MRD. The interviews will be conducted through a single focus group and several face-to- face interviews or performed online, using ZOOM. Participants should have more than one year of experience post-residency or post-fellowship training. The predetermined set of semi- structured questions will cover topics such as the definition of MRD, its clinical and research significance, MRD detection thresholds, duration of MRD negativity, and its correlation with other clinical endpoints, such as progression-free survival and overall survival. The interviews will be conducted by scientific oncology and hematology evaluation experts at the Saudi Food and Drug Authority, who play a crucial role in this study. The study will consist of 5–10 semi- structured one-to-one interviews and focused group discussions of as few as four participants. Before starting any interview, participants will complete consent forms, including the study’s goals and who will conduct the study. Qualitative data will be prepared and analyzed by an expert in data analysis, ensuring the highest research standards. The results will be presented using descriptive and interpretive methods. Citation Format: Albandari A Alnasser, Tariq H Alqurayshah. Qualitative research study on the use of minimal residual disease as an intermediate endpoint in multiple myeloma clinical trials in Saudi Arabia [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B006.

Comparative clinical evaluation of correct anatomic contour and tight contact in Class II direct composite restoration using two newer contact forming instruments

Aim: The aim of the study was to compare and evaluate proximal contact tightness and contours using two newer contact-forming systems in Class II composite restorations. Materials and Methods: After institutional ethical approval and Clinical Trials Registry-India registration, patients were chosen according to the inclusion-exclusion criteria with informed consent. A total of 60 patients were randomly assigned to two groups. Group A: LM Arte contact former (n = 30) and Group B: The design village (TDV) contact former (n = 30). Quadrant isolation was performed after the complete elimination of dental caries, preceded by the insertion of a matrix band and retainer with the proper wedging system. The LM Arte with the appropriate tip was selected for Group A, whereas the TDV contact former was selected for Group B based on the cavity size. Following the conversion of Class II cavities to Class I, nanohybrid resin composite restoration was done by cuspal layering. It was followed by finishing and polishing. E. B. Hencock criteria were used to evaluate gingival index, pocket depth, interproximal calculus, overhangs, food impaction, and contact integrity in both groups at baseline, 6 months, and 1 year. Statistical Methods: The data were analyzed using the Chi-Square test with SPSS (Statistical Package for Social Sciences) software version 18.0, IBM. Results: A statistically significant reduction in gingival index score was observed in both groups 6 months and 1 year after the procedure. However, the values revealed in terms of gingival index (P < 0.05) and (P > 0.05) for pocket depth, interproximal calculus, overhangs, food impaction, and contact integrity in both groups for 6 months (P > 0.05) and (P > 0.05) after the procedure. Conclusion: Both the LM Arte and TDV contact-forming systems are effective in establishing perfect proximal contacts and contours. However, the LM Arte contact-forming system edges out the TDV contact-forming system.

Cardiovascular Events After Chimeric Antigen Receptor T-Cell Therapy for Advanced Hematologic Malignant Neoplasms

The frequency and clinical phenotypes of cardiotoxic events in chimeric antigen receptor (CAR) T-cell recipients remain poorly understood given that landmark approval trials typically exclude patients with high-risk cardiovascular profiles and data from nontrial settings are scarce. To summarize the prevalence of adverse cardiovascular events among adults receiving CAR T-cell therapies for advanced hematologic malignant neoplasms. MEDLINE, Embase, Cochrane Library, and Google Scholar were systematically searched from database inception until February 26, 2024. Observational studies were included if they comprised adult CAR T-cell recipients with advanced hematologic malignant neoplasms and if they systematically evaluated cardiovascular complications. Extraction of prespecified parameters related to the patient population, study design, and clinical events was performed at the study level by 2 independent reviewers in accordance with the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Meta-analysis of single proportions was conducted using random-effect models with Freeman-Tukey double arcsine transformations to calculate pooled prevalence estimates. Sensitivity analysis was performed using generalized linear mixed models with logit transformations. Ventricular and supraventricular arrhythmias, heart failure events, reduction in left ventricular ejection fraction, myocardial infarction, and cardiovascular and all-cause mortality. Thirteen studies comprising 1528 CAR T-cell recipients (median [IQR] age, 61 [58.7-63.0] years; 1016 males [66%]; 80% patients with lymphoma) were included. The median (IQR) duration of follow-up was 487 (294-530) days. On random-effects meta-analysis, we observed a pooled prevalence of 0.66% (95% CI, 0.00%-2.28%) for ventricular arrhythmia, 7.79% (95% CI, 4.87%-11.27%) for supraventricular arrhythmia, 8.68% (95% CI, 2.26%-17.97%) for left ventricular dysfunction, 3.87% (95% CI, 1.77%-6.62%) for heart failure events, 0.62% (95% CI, 0.02%-1.74%) for myocardial infarction, and 0.63% (95% CI, 0.13%-1.38%) for cardiovascular death. The pooled prevalence of all-cause mortality was 30.01% (95% CI, 19.49%-41.68%). Sensitivity analyses generated similar findings. This meta-analysis found a low prevalence of ventricular arrhythmia, myocardial infarction, and cardiovascular death among CAR T-cell recipients over a short-term to midterm follow-up. Left ventricular dysfunction and supraventricular arrhythmia were the most commonly reported cardiovascular complications, suggesting that cardiovascular surveillance strategies should focus on decreases in ejection fraction and supraventricular arrhythmia.

Hybrid versus catheter ablation for Hypertrophic CardioMyopathy with Atrial Fibrillation (HCM-AF): study protocol for a randomised controlled trial

IntroductionAtrial fibrillation (AF) is an independent predictor of adverse outcomes in patients with hypertrophic cardiomyopathy (HCM). Although catheter ablation is highly recommended for general AF populations, it is less effective...

Exploring the Insights on Exosomes and their Utility in Treating Ophthalmic Disease: Delving into the Clinical Approval and Present Trials.

Ophthalmic diseases include a wide array of conditions, each requiring individualized treatment approaches. In ophthalmic research and as therapeutics against potential pharmacological indications, several subtypes of exosomes (EVs) have been reconnoitered, mainly for their regenerative, neuroprotective, and anti-inflammatory characteristics. EVs are recently gaining wider attention as promising vehicles for therapies because of their natural participation in communication between cells and targeted delivery. These small vesicles, derived from cells, transport numerous molecules between cells, thus contributing advantages like low immunogenicity, stability, and the ability to target cells specifically. These inherent advantages of carrying the therapeutic cargo and enabling intercellular signaling make them a captivating avenue for progressing ophthalmic disease treatment options. While research is ongoing, and clinical applications are still emerging, several EV subtypes have shown promise for possible applications in addressing several ophthalmic diseases, such as glaucoma, age-related macular degenerative disorders, retinal degenerative disorders, and ocular inflammatory conditions.

Accelerated Approval for Cancer Drugs in the United States and the Clinical Evidence Required for Conversion to Regular Approval

PurposeOncology products often leverage accelerated approval program to seek earlier launches in the United States. Little is known about how the Food and Drug Administration (FDA) has been balancing evidence and access, and the factors that may characterize post-accelerated approval requirements. The present study aimed to obtain insights on how accelerated approval is determined by investigating the balance between pre-accelerated approval and supplemental clinical evidence required for future regular approval.MethodsThe product properties, pre-accelerated approval evidence, rationale, post-accelerated approval requirements, and prior regulatory designations for oncology accelerated approvals were summarized based on public databases. Regression analyses were performed to investigate factors that may have been associated with the post-accelerated approval requirements.ResultsHundred fifty-seven accelerated approvals were granted between 1992 and 2021. An increase in the number of pre-accelerated approval trials by one trial resulted in a 20% decrease in supplemental trials. The endpoint for the post-accelerated approval trial tended to be more robust when products were indicated for common cancers, while less robust when products had been used to treat fewer subjects, when products were indicated for respiratory and skin cancers, or when less malignant cancers were targeted.ConclusionsAccelerated approvals for oncology products were often based on the response rate of a noncomparative trial. However, considerable variation was observed in the post-accelerated approval requirements. Factors such as the quality and quantity of pre-accelerated approval evidence, regulatory designations, and operational feasibility may have been considered when determining the accelerated approvals and post-accelerated approval requirements.

Dosage Optimization: A Regulatory Perspective for Developing Oncology Drugs.

Optimized dosages provide a secure foundation for the development of well-tolerated and effective oncology drugs. Project Optimus, an initiative within the Oncology Center of Excellence, strives to reform the dosage optimization and dosage selection paradigm in oncology. This initiative stems from the availability of targeted drugs and from the demand for more tolerable dosages from patients, caregivers, and advocates. Reforming dosage optimization for oncology drugs requires a paradigm shift from the one employed for cytotoxic chemotherapy to one that understands and considers the unique attributes of targeted therapy, immunotherapy, and cellular therapy. Limited characterization of dosage during drug development may result in (1) patients not staying on a therapy long-term due to poor tolerability, (2) failure to establish positive benefit-risk in clinical trials for regulatory approval (3) withdrawal of drugs from the market (4) removal of indications of drugs from the market. Timely access to drugs is important for all patients with cancer, so it is vital to iteratively analyze all nonclinical and clinically relevant data at each stage of development and leverage quantitative approaches, innovative trial designs, and regulatory support to arrive at dosages with favorable benefit-risk. This review highlights the key challenges and opportunities to embracing this new paradigm and realizing the full potential of new oncology therapies.

Practice patterns and predictors of treatment intensification in patients with metastatic castration-sensitive prostate cancer.

Treatment intensification beyond androgen deprivation therapy (ADT) has shown survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC). There is a need to better understand how these novel treatments fit in real-world practice. Using electronic medical records and administrative data, a population-based, retrospective cohort study of patients newly diagnosed with de novo mCSPC between 2010 and 2020 in Alberta, Canada, and initiated ADT was conducted. Treatment intensification was defined as the receipt of apalutamide, abiraterone acetate, enzalutamide, or chemotherapy (e.g., docetaxel) within 180 days of ADT initiation. A total of 2515 de novo mCSPC were identified, with 2098 (83%) patients initiating ADT post-diagnosis. Of those, 525 (25%) received intensification beyond ADT. The percentage of patients who were intensified was 3% in 2010-2013 and gradually increased to 67% in 2020. From 2014-2017, docetaxel was the most commonly used approach, although it was supplanted by abiraterone acetate, apalutamide and enzalutamide from 2018 onwards. In multivariable logistic regression analyses of patients diagnosed from 2014-2020, significant predictors of intensification were younger age at diagnosis, lower Charlson comorbidity index, greater number of metastatic sites, shorter time to ADT initiation, referral to a medical oncologist, transurethral resection of the prostate or radiation prior to ADT, and more recent year of diagnosis (all p<0.05). Intensification increased for patients living in rural areas and with higher disease burden in 2018+ compared to 2014-2017. There has been a considerable increase in the use of ADT intensification therapies that correspond with the timing of clinical trial data and approvals of novel agents.

Artificial intelligence algorithms permits rapid acute kidney injury risk classification of patients with acute myocardial infarction

ObjectiveThis study aimed to develop and validate several artificial intelligence (AI) models to identify acute myocardial infarction (AMI) patients at an increased risk of acute kidney injury (AKI) during hospitalization. MethodsIncluded were patients diagnosed with AMI from the Medical Information Mart for Intensive Care (MIMIC) III and IV databases. Two cohorts of AMI patients from Changzhou Second People's Hospital and Xuzhou Center Hospital were used for external validation of the models. Patients' demographics, vital signs, clinical characteristics, laboratory results, and therapeutic measures were extracted. Totally, 12 AI models were developed. The area under the receiver operating characteristic curve (AUC) were calculated and compared. ResultsAKI occurred during hospitalization in 1098 (28.3 %) of the 3882 final enrolled patients, split into training (3105) and test (777) sets randomly. Among them, Random Forest (RF), C5.0 and Bagged CART models outperformed the other models in both the training and test sets. The AUCs for the test set were 0.754, 0.734 and 0.730, respectively. The incidence of AKI was 9.8 % and 9.5 % in 2202 patients in the Changzhou cohort and 807 patients in the Xuzhou cohort with AMI, respectively. The AUCs for patients in the Changzhou cohort were RF, 0.761; C5.0, 0.733; and bagged CART, 0.725, respectively, and Xuzhou cohort were RF, 0.799; C5.0, 0.808; and bagged CART, 0.784, respectively. ConclusionSeveral machines learning-based prediction models for AKI after AMI were developed and validated. The RF, C5.0 and Bagged CART model performed robustly in identifying high-risk patients earlier. Clinical trial approval statementThis Trial was registered in the Chinese clinical trials registry: ChiCTR1800014583. Registered January 22, 2018 (http://www.chictr.org.cn/searchproj.aspx).

Biologics and Small Molecule Targeted Therapies for Pediatric Alopecia Areata, Psoriasis, Atopic Dermatitis, and Hidradenitis Suppurativa in the US: A Narrative Review.

The management of pediatric dermatological conditions such as alopecia areata (AA), psoriasis, atopic dermatitis (AD), and hidradenitis suppurativa (HS) has significantly evolved with the introduction of biologics and small molecule targeted therapies. The advancement in understanding the immunopathogenesis of these chronic skin conditions has led to the development and approval of novel biologics and small molecule therapies. Initially approved by the United States Food and Drug Administration (FDA) for adults, most of these therapies are now being evaluated in clinical trials for safety and efficacy in adolescents and children, expanding new treatment options for pediatric patients. The role of the FDA in drug approval is multifaceted from drug inception, ensuring that research, data, and evidence show that the proposed drug is effective and safe for the intended use. The goal of this review article is to provide an overview of the recently FDA-approved and potential biologic and oral small molecule therapies in clinical trials for AA, psoriasis, AD, and HS in pediatric patients. The search for this review included keywords in ClinicalTrials.gov, PubMed, and Google Scholar for the latest research and clinical trials relevant to these conditions and treatments without the PRISMA methodology. For pediatric AA, ritlecitinib is FDA-approved, while baricitinib and updacitinib are in phase 3 clinical trials for pediatric approval. The FDA-approved drugs for pediatric psoriasis include secukinumab, ustekinumab, ixekizumab, etanercept, and apremilast. Other phase 3 clinical trials for pediatric psoriasis include risankizumab, guselkumab, tildrakizumab, brodalumab, and deucravacitinib. For pediatric AD, the FDA-approved drugs are dupilumab, tralokinumab, abrocitinib, and upadacitinib, with many other drugs in phase 3 trials. Adalimumab is an FDA-approved biologic for pediatric HS, with various clinical trials ongoing for adults. The approved biologics and small molecule therapies had higher efficacy and improved safety profiles compared to traditional medications. With numerous ongoing trials, the success of these clinical trials could lead to their inclusion in treatment guidelines for these chronic skin conditions. Biologics and small molecule therapies offer new avenues for effective disease management, enabling personalized therapeutic interventions and improving pediatric health outcomes.

Characteristics of Clinical Trials for the US Food and Drug Administration Accelerated Approval and Subsequent Confirmatory Trials: Implications for Drug Approval in Japan.

The Accelerated Approval (AA) Program of the United States (US) Food and Drug Administration (FDA) was established to facilitate and expedite access to new drugs for serious or life-threatening conditions. Although many drugs have granted AAs in the US, the number of approvals under the conditional approval system in Japan remains limited. This study aimed to examine whether confirmatory trials after the US AA are conducted in accordance with the design of postmarketing requirements and assess the timing of regular approval (RA) in Japan for drugs that have been granted US AA. Utilizing FDA databases and Japanese regulatory data from 1992 to 2023, we analyzed indications, postmarketing requirements, and clinical trial designs. Our findings indicate that the AA program in the US is well-managed as most AAs were converted to RAs based on confirmatory study data that met the designations. From the Japanese perspective, our findings show that the over half of Japanese RAs can be obtained without waiting for confirmatory trial results. By granting RA, instead of conditional approval, based on exploratory trial data in the US AA, the opportunity to evaluate postmarketing confirmatory trial results might be lost in Japan. Therefore, further improvements are needed to actively utilize the conditional approval system, which could allow for the rapid introduction of innovative drugs and also the verification of their efficacy and safety at an appropriate time.

Physical literacy-based intervention for older adults: a cluster randomized controlled trial study protocol.

The ageing population creates concerns and challenges worldwide. The large number of older adults (aged over 65) in Hong Kong continues to rise as people live longer. This may result in heavy burdens on public services and problems such as a shortage of medical resources. The purpose of this study is to implement a physical literacy-based intervention among older adults in Hong Kong in order to achieve the goal of health promotion. A two-arm cluster randomized controlled trial will be employed in this proposed study. Ten daycare centers for the older adults in Hong Kong will be invited to participate in this study. The intervention group will receive functional fitness training and mastering physical literacy class twice a week with buddy peer support, and they will be asked to keep a reflective writing journal on a daily basis for 12 weeks in total. Participants will be evaluated at baseline (week 0), post-intervention (week 12), and at 6-week follow-up (week 18). This will consist of objective and self-reported measures covering elements within physical literacy (i.e., physical competence, motivation and confidence, knowledge and understanding) and also physical activity levels on an individual basis. The study intends to introduce a conceptual framework of physical literacy for the older adults through an intervention that allows older people to develop daily behaviour habits, which should promote active ageing for the older adults and greater self-esteem in later life. After this study, participants may share their positive experiences, and encourage their peers in the community to become physically literate in the future. In the long run, due to the feasibility and sustainability of these potential programs, this proposed study has the potential to connect seniors through social engagement and contribute to healthy living. Clinical trial approval from the National Library of Medicine (Reference number: NCT06137859).

Challenges for novel antiretroviral development in an era of widespread TLD availability.

Over 80% of people living with HIV in low-and-middle-income countries (LMICs) take first-line TDF/XTC/DTG (TLD). Due to hard-fought activism, in >100 LMICs TLD now costs under $45pppy under Voluntary License. With final DTG patents expiring by 2029, generic TLD will soon be available globally. We identify seven critical benchmarks underpinning TLDs success which novel ART should now meet, and an eighth for which novel ART should aim. These are superior efficacy; a high genetic barrier to resistance; safety in hepatitis B coinfection; favourable drug-drug interaction profiles including with antimycobacterials; efficacy in HIV-2; safety in pregnancy, long-acting formulation availability and affordable pricing from the outset. We illustrate when generic TLD will become available worldwide and compare this with trial programmes and approval timelines for two case-study novel ART combinations: islatravir/doravirine and cabotegravir/rilpivirine. We demonstrate that currently these regimens and trial programmes will not meet key benchmarks required to compete with TLD.

Skin graft surgery and its impact on platelet counts in Iranian burn patients: a non-randomized clinical trial

BackgroundPlatelets are critical in maintaining homeostasis and immune response in burn patients. The concentration of platelets decreases in burn patients, and any intervention that increases serum platelet concentration can prevent serious consequences and patient death. The present study aimed to assess the impact of skin graft surgery on burn patients’ platelet counts.MethodsIn this non-randomized clinical trial, 200 burn patients were investigated. The patients were recruited from the surgical ward of Imam Khomeini Teaching Hospital during the first six months of 2021. After completing the checklist, patients underwent skin graft surgery. Blood was taken from the patients during surgery in the operating room and on the third and fifth day after the surgery to check platelets. Data analysis was conducted using SPSS software (ver. 22.0).ResultsMost patients (63.5%) were male, and 73 (36.5%) were female. One hundred eighty-one patients (90.5%) had deep burns, and 19 (9.5%) had superficial burns. The mean burns percentage in the patients was 19.3 ± 15.4%, the lowest was 2%, and the highest was 90%. The most common burns were caused by flame (42%) and boiling water (30.5%). The patients’ outcomes revealed that 6% gained complete recovery, 86.5% partial recovery, 2.5% showed transplant rejection, and 5% died. Mean platelet levels in deceased patients had an upward trend. The mean platelet counts of patients were elevated during surgery (289,855 ± 165,378), decreased three days after surgery (282,778 ± 317,310), and elevated again five days after surgery (330,375 ± 208,571). However, no significant difference was found between the mean platelet counts during surgery, the third and fifth days after surgery in patients undergoing skin grafts (P = 0.057).ConclusionsThis study suggests that skin graft positively increases the patient’s platelets. Further studies are needed to confirm the findings and elucidate the mechanism. Iranian Registry of Clinical Trial approval code (IRCT# IRCT20131112015390N8 & 06/01/2024).

Effects of individualised lung-protective ventilation with lung dynamic compliance-guided positive end-expiratory pressure titration on postoperative pulmonary complications of paediatric video-assisted thoracoscopic surgery: protocol for a randomised controlled trial

IntroductionLung-protective ventilation strategies (LPVS) for one-lung ventilation (OLV) in paediatric patients pose greater challenges than in adults. Optimising LPVS for paediatric OLV to mitigate postoperative pulmonary complications (PPCs) has emerged...

OTHR-29. A SINGLE INSTITUTION REVIEW REGARDING TRENDS IN THE MOLECULAR ANALYSIS OF PEDIATRIC CENTRAL NERVOUS SYSTEM (CNS) TUMORS AND GERMLINE ANALYSIS BETWEEN 2019 – 2023, EMPHASIZING THE IMPORTANCE OF EASY ACCESS TO COMPREHENSIVE TESTING

Abstract BACKGROUND Molecular characterization of pediatric CNS tumors improves diagnostic accuracy and guides treatment. Germline analysis is also important to uncover cancer predisposition syndromes, which influence the approach to treatment and tumor surveillance. The options for molecular assessment are influenced by availability, including access through a trial or insurance approval. METHODS A retrospective review of the molecular workup performed on all CNS tumors biopsied/resected at Children’s Minnesota from 2019 – 2023 was undertaken to look at trends in the specific tests performed over time and how the molecular results guided treatment. RESULTS Between 2019 – 2023, 220 patients at Children’s Minnesota were diagnosed with a CNS tumor. A total of 191 underwent surgery and 162 (85%) had sufficient tissue for molecular analysis. There was no apparent difference in the percentage of patients who underwent IHC/FISH/NGS between 2019 - 2023, but methylation profiling frequency increased over time (2019 2%, 2020 and 2021 10%, 2022 58% and 2023 71%). Frequency of germline analysis also increased (2019-2021 29%, 2022-52% and 2023-63%). Easy availability of comprehensive molecular and germline analysis for patients enrolled on COG-APEC14B1 is credited for these improving trends. Molecular analysis confirmed (59%) or supported (36%) the diagnosis, and guided treatment in 30% of cases (stratification of treatment in 89% of medulloblastoma and targeted treatment in 63% of high-grade glioma, 9% of medulloblastoma and 6% of low-grade glioma). Methylation profiling alone accurately diagnosed 79% of cases, including subtyping tumors. Germline analysis detected a pathogenic germline alteration in 14% of CNS tumor patients (NF1 5%; TP53 and BRIP1 1%; PALB1, NF2, TS2, SMARCB1, biallelic PMS2, CHEK2, FANCA, ORICH1 and SDHA 0.5%). CONCLUSION These findings demonstrate the importance of easy access to comprehensive molecular and germline analysis with quick turnaround time to provide the best diagnosis, prognosis and treatment options for pediatric CNS tumor patients.

RETRACTION: Comparative effectiveness of low-level laser therapy and transcutaneous electrical nerve stimulation in symptomatic Temporomandibular Disorders: A Randomised Control Trial.

Batra, S. Srivastava, A., Shivakumar, G. C., Marrapodi, M. M., Herford, A. S., Cicciù, M., Minervini, G. (2023) Comparative effectiveness of low-level laser therapy and transcutaneous electrical nerve stimulation in symptomatic Temporomandibular Disorders: A Randomised Control Trial. Journal of Oral Rehabilitation, 50: 1185-1193. https://doi.org/10.1111/joor.13555 The above article, published online on 05 July 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Peter Svensson, and John Wiley and Sons Ltd. The retraction has been agreed following concerns raised by a third party about the ethical approval for the study described. The publisher contacted the authors, who provided a letter of ethical approval from People's College of Dental Sciences & Research Center, People's University, which did not match the ethical approval reported in the article. The authors reported that the study was initiated at Banaras Hindu University, but were not able to provide evidence of ethical approval from this institution. In addition, the authors did not provide an explanation for why the clinical trial was registered with Clinical Trial Registry-India retrospectively, which violates the journal's author guidelines that require authors to provide an explanation for retrospective registration of clinical trials. Following the investigation by the publisher, the journal has concluded this article did not follow the journal's requirements regarding ethical approval of clinical trials and registration of clinical trials, and so the journal must issue a retraction. Shivakumar, G. C. has stated that Marrapodi, M. M., Herford, A. S., Cicciù, M., and Minervini, G. were not involved in the investigation, data curation, conceptualization, methodology, or formal analysis of the clinical study. The authors disagree with this retraction.